U.S. patent number 10,954,544 [Application Number 16/691,737] was granted by the patent office on 2021-03-23 for biosensor for multi-analyte characterization.
This patent grant is currently assigned to INTERNATIONAL BUSINESS MACHINES CORPORATION. The grantee listed for this patent is INTERNATIONAL BUSINESS MACHINES CORPORATION. Invention is credited to Hariklia Deligianni, Bruce B. Doris, Steven J. Holmes, Qinghuang Lin, Roy R. Yu.
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United States Patent |
10,954,544 |
Deligianni , et al. |
March 23, 2021 |
Biosensor for multi-analyte characterization
Abstract
Embodiments of the present invention are directed to a
semiconductor device. A non-limiting example of the semiconductor
device includes a semiconductor substrate. The semiconductor device
also includes a plurality of metal nanopillars formed on the
substrate. The semiconductor device also includes an amperometric
sensor associated with one of the plurality of nanopillars, wherein
the amperometric sensor is selective to an enzyme-active
neurotransmitter. The semiconductor device also includes a
resistivity sensor associated with a pair of nanopillars, wherein
the resistivity sensor is selective to an analyte.
Inventors: |
Deligianni; Hariklia (Alpine,
NJ), Doris; Bruce B. (Slingerlands, NY), Holmes; Steven
J. (Ossining, NY), Lin; Qinghuang (Yorktown Heights,
NY), Yu; Roy R. (Poughkeepsie, NY) |
Applicant: |
Name |
City |
State |
Country |
Type |
INTERNATIONAL BUSINESS MACHINES CORPORATION |
Armonk |
NY |
US |
|
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Assignee: |
INTERNATIONAL BUSINESS MACHINES
CORPORATION (Armonk, NY)
|
Family
ID: |
1000005438649 |
Appl.
No.: |
16/691,737 |
Filed: |
November 22, 2019 |
Prior Publication Data
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Document
Identifier |
Publication Date |
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US 20200087700 A1 |
Mar 19, 2020 |
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Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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15671938 |
Aug 8, 2017 |
10752932 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
C12Q
1/001 (20130101); C12Y 113/12004 (20130101); C12Y
101/03017 (20130101); G01N 33/9406 (20130101); C12Y
101/03004 (20130101); G01N 27/327 (20130101); C12Y
104/03011 (20130101); C12Q 1/005 (20130101); G01N
2333/90241 (20130101); G01N 2333/90638 (20130101); G01N
33/9413 (20130101); G01N 2333/904 (20130101) |
Current International
Class: |
C12Q
1/00 (20060101); G01N 27/327 (20060101); G01N
33/94 (20060101) |
Field of
Search: |
;204/400
;977/773,742,902 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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Oct 2005 |
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Dec 2010 |
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JP |
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2012053656 |
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Mar 2012 |
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JP |
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2013178601 |
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Sep 2013 |
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JP |
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2013202481 |
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Oct 2013 |
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JP |
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Other References
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Single-Trial Activities of Multiple Neurons in Monkey Superior
Colliculus", Neurosci. Res. Inst., ICONIP 2007, Part II, LNCS 4985,
pp. 997-1006, 2008. cited by applicant .
Hernandez et al., "Template Fabrication of Protein-Functionalized
Gold-Polypyrrole--Gold Segmented Nanowires", Chem. Mater. 2004, 16,
pp. 3431-3438. cited by applicant .
Jeon et al., "Electrically Actuatable Smart Nanoporous Membrane for
Pulsatile Drug Release", Nano Lett. 2011, 11, pp. 1284-1288. cited
by applicant .
Kan et al., "Imprinted electrochemical sensor for dopamine
recognition and determination based on a carbon nanotube /
polypyrrole film" Electrochimica Acta 63 (2012) pp. 69-75. cited by
applicant .
Kumpangpet et al., "Fabrication of Gold Nanoparticles / Polypyrrole
/ HRP Electrode for Phenol Biosensor by Electropolymerization",
Engineering Journal, vol. 16, Issue 3; Received Nov. 17, 2011;
Accepted May 7, 2012; Published Jul. 1, 2012; Online at
http://www.engj.org/; pp. 45-52. cited by applicant .
List of IBM Patents or Patent Applications Treated as Related; Date
Filed: Nov. 22, 2019, 2 pages. cited by applicant .
Maouche et al., "Molecularly imprinted polypyrrole films: Some key
parameters for electrochemical picomolar detection of dopamine",
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by applicant .
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polypyrrole for the antibiotic levofloxacin", Thin Solid Films 520
(2012) pp. 1938-1943. cited by applicant .
Qin et al., "Microsensors for in vivo Measurement of Glutamate in
Brain Tissue"; Sensors 2008, 8, DOI: 10.3390/s8116860;
http://www.mdpi.com/journal/sensors; pp. 6860-6884. cited by
applicant .
Ryohei P. Hasegawa, et al., "Single trial-based prediction of a
go/no-go decision in monkey superior colliculus", ScienceDirect,
(Received Jan. 13, 2006); accepted May 8, 2006, Neural Networks 19
(2006) 1223-1232. cited by applicant .
Schneider, Elizabeth "Oriented Attachment of Cytochrome P450 2C9 to
a Self-Assembled Monolayer on a Gold Electrode as a Biosensor
Design"; Electronic Theses and Dissertations UC Berkeley;
Acceptance Date: Fall 2011; 108 pgs. cited by applicant .
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Polypyrrole Film for Sensing of Clofibric Acid" Sensors 2015, 15,
doi: 10.3390/s150304870; www.mdpi.com/journal/sensors; ISSN
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cited by applicant .
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measurement in rat striatum"; Sensors and Actuators B 171-172
(2012) pp. 93-101. cited by applicant .
Yan, et al., "Characteristic and Synthetic Approach of Molecularly
Imprinted Polymer," Int. J. Mol. Sci. 2006, 7, 155-178; (24 pages).
cited by applicant.
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Primary Examiner: Han; Jonathan
Attorney, Agent or Firm: Cantor Colburn LLP Curro;
Anthony
Parent Case Text
DOMESTIC PRIORITY
This application is a divisional of U.S. application Ser. No.
15/671,938, titled "Biosensor for Multi-Analyte Characterization"
filed Aug. 8, 2017, the contents of which are incorporated by
reference herein in its entirety.
Claims
What is claimed is:
1. A computer-implemented method of multi-analyte detection, the
method comprising: receiving, by a processor, a signal from a
multi-analyte sensor in contact with a biological tissue, wherein
the multi-analyte sensor comprises a resistivity sensor and an
amperometric sensor, wherein the resistivity sensor comprises a
first nanopillar, a second nanopillar, and an imprinted polymer in
direct contact with an upper portion of the first nanopillar and an
upper portion of the second nanopillar; determining, by the
processor, a resistivity value from the resistivity sensor;
generating, by the processor, a concentration of a first analyte
based at least in part upon the resistivity value; determining, by
the processor, an electrical current from the amperometric sensor;
and generating, by the processor, a concentration of a second
analyte based at least in part upon the electrical current.
2. The computer-implemented method of claim 1, wherein the
biological tissue comprises neuronal tissue.
3. The computer-implemented method of claim 1, wherein the first
analyte is dopamine.
4. The computer-implemented method of claim 1, wherein the second
analyte comprises an enzyme-active neurotransmitter.
5. The computer-implemented method of claim 4, wherein the
amperometric sensor is selective to the enzyme-active
neurotransmitter.
6. The computer-implemented method of claim 5, wherein the
enzyme-active neurotransmitter is selected from the group
consisting of glutamate, lactate, glucose, choline, adenosine, and
gamma-amino-butyric acid (GABA).
7. The computer-implemented method of claim 6, wherein the
enzyme-active neurotransmitter comprises glutamate.
8. The computer-implemented method of claim 7, wherein determining
the electrical current comprises measuring the electrical current
from a decomposition of Glutimate.
9. The computer-implemented method of claim 1, wherein the
amperometric sensor comprises a conductive porous polymer.
10. The computer-implemented method of claim 9, wherein the
conductive porous polymer comprises a polymer selected from the
group consisting of polyaniline, polypyrrole,
poly(3,4-ethylenedioxythiophene), and mixtures thereof.
11. The computer-implemented method of claim 10, wherein the
conductive porous polymer further comprises a miscibility
additive.
12. A computer-implemented method of multi-analyte detection, the
method comprising: providing a multi-analyte sensor comprising a
sensing layer formed on an interface layer, the sensing layer
comprising an array of alternating chemical sensors, the array of
alternating chemical sensors comprising a first sensor type and a
second sensor type, wherein the first sensor type comprises a
resistivity sensor and the second sensor type comprises an
amperometric sensor, wherein the resistivity sensor comprises a
first nanopillar, a second nanopillar, and an imprinted polymer in
direct contact with an upper portion of the first nanopillar and an
upper portion of the second nanopillar; providing a processor
communicatively coupled to the multi-analyte sensor; receiving, by
the processor, a resistivity value from the resistivity sensor;
generating, by the processor, a concentration of a first analyte
based at least in part upon the resistivity value; receiving, by
the processor, an electrical current from the amperometric sensor;
and generating, by the processor, a concentration of a second
analyte based at least in part upon the electrical current.
13. The computer-implemented method of claim 12, wherein each of
the chemical sensors are formed on a top surface of a
nanopillar.
14. The computer-implemented method of claim 12 further comprising
contacting the multi-analyte sensor with a biological tissue.
15. The computer-implemented method of claim 14, wherein the
biological tissue comprises neuronal tissue.
16. The computer-implemented method of claim 12, wherein the first
analyte is dopamine.
17. The computer-implemented method of claim 12, wherein the second
analyte comprises an enzyme-active neurotransmitter.
18. The computer-implemented method of claim 17, wherein the
amperometric sensor is selective to the enzyme-active
neurotransmitter.
19. The computer-implemented method of claim 18, wherein the
enzyme-active neurotransmitter is selected from the group
consisting of glutamate, lactate, glucose, choline, adenosine, and
gamma-amino-butyric acid (GABA).
20. The computer-implemented method of claim 19, wherein the
enzyme-active neurotransmitter comprises glutamate.
Description
BACKGROUND
The present invention generally relates to fabrication methods and
resulting structures for biosensors. More specifically, the present
invention relates to biosensors for multi-analyte
characterization.
Biosensors can be useful for the detection and characterization of
biomolecules. There exist a variety of different types of bio
sensors, including calorimetric biosensors, potentiometric
biosensors, acoustic wave biosensors, amperometric biosensors, and
optical biosensors. Biosensors can be tailored to sense a specific
analyte for specific applications. For instance, specific
neurotransmitters, such as dopamine, can be detected in vivo for
the study of neurological disorders.
Many biological processes, disorders, and diseases simultaneously
implicate actions and interactions of a plurality of biomolecules.
Studies of the interplay and relationships between such molecules
can require sensing of multiple analytes. Moreover, the location of
such biomolecules can be an important factor in biological
function. For example, in the case of neurotransmitters,
neurotransmitters can travel across a short distance of a synapse
and the locations of such neurotransmitters can play an important
role in understanding neurological processes. In addition, a neuron
can have a length of from about 10 to 100 microns and, depending on
biological state, different biomolecules can be present at
different locations along the neurotransmitter. In such
applications, multi-analyte sensing capability and biosensors with
nanoscale resolution can provide valuable information.
SUMMARY
Embodiments of the present invention are directed to a method for
fabricating a semiconductor device. A non-limiting example of the
method includes forming a plurality of nanopillars on a substrate,
the plurality of nanopillars including a first nanopillar and a
pair of adjacent nanopillars. The method also includes forming an
insulating layer on the plurality of nanopillars to generate a
plurality of lined nanopillars. The method also includes removing
the insulating layers from upper portions of the pair of adjacent
nanopillars to generate exposed adjacent nanopillar portions. The
method also includes forming a resistivity sensor on the exposed
adjacent nanopillar portions. The method also includes removing the
insulating layer from the first nanopillar to generate an exposed
first nanopillar portion. The method also includes forming an
amperometric sensor on the exposed first nanopillar portion. Such
embodiments of the invention can advantageously form a
semiconductor device with multi-analyte sensing capability that can
provide nanoscale resolution.
Embodiments of the present invention are directed to a
semiconductor device. A non-limiting example of the semiconductor
device includes a semiconductor substrate. The semiconductor device
also includes a plurality of metal nanopillars formed on the
substrate. The semiconductor device also includes an amperometric
sensor associated with one of the plurality of nanopillars, wherein
the amperometric sensor is selective to an enzyme-active
neurotransmitter. The semiconductor device also includes a
resistivity sensor associated with a pair of nanopillars, wherein
the resistivity sensor is selective to an analyte. Such embodiments
of the invention can advantageously sense multiple biological
analytes simultaneously and in real-time.
Embodiments of the present invention are directed to a
multi-analyte biosensor. A non-limiting example of the biosensor
includes a substrate. The biosensor also includes a first
nanopillar including a base connected to the substrate. The
biosensor also includes a second nanopillar including a base
connected to the substrate, wherein the second nanopillar is
adjacent to the first nanopillar. The biosensor also includes an
imprinted polymer physically contacting at least a portion of the
first nanopillar and at least a portion of the second nanopillar,
wherein the imprinted polymer includes a conductive porous polymer
including a plurality of cavities with affinity to a first analyte.
The biosensor also includes a third nanopillar including a base
connected to the substrate, wherein the third nanopillar is lined
with an amperometric sensor polymer including a plurality of
binding sites with affinity to a second analyte. Such embodiments
can advantageously detect both enzymatic and non-enzymatic
biological analytes in a biological tissue sample.
Embodiments of the present invention are directed to a
multi-analyte biosensor. A non-limiting example of the biosensor
includes a semiconductor substrate. The multi-analyte biosensor
also includes a first sensing region including a first plurality of
nanopillars connected to a first conductive polymer selective to a
first biomolecule, wherein the first sensing region is connected to
the semiconductor substrate. The multi-analyte biosensor also
includes a second sensing region including a second plurality of
nanopillars connected to a second conductive polymer selective to a
second biomolecule, wherein the second sensing region is connected
to the semiconductor substrate and wherein the second biomolecule
is different than the first biomolecule. The multi-analyte
biosensor also includes an interface layer connecting the
semiconductor substrate to a processor. The multi-analyte biosensor
also includes a communications interface. Such embodiments can
advantageously sense multiple analytes and their positional
information in real time and provide concentration and position
information to a user.
Embodiments of the invention are directed to a computer-implemented
method of multi-analyte detection. A non-limiting example of the
method includes receiving, to a processor, a signal from a
multi-analyte sensor in contact with a biological tissue, wherein
the multi-analyte sensor includes a resistivity sensor and an
amperometric sensor. The method also includes determining, by the
processor, a resistivity value from the resistivity sensor. The
method also includes generating, by the processor, a concentration
of a first analyte based at least in part upon the resistivity
value. The method also includes determining, by the processor, an
electrical current from the amperometric sensor. The method also
includes generating, by the processor, a concentration of a second
analyte based at least in part upon the electrical current. Such
embodiments can advantageously determine the concentration of
multiple analytes at nanoscale resolution.
Additional technical features and benefits are realized through the
techniques of the present invention. Embodiments and aspects of the
invention are described in detail herein and are considered a part
of the claimed subject matter. For a better understanding, refer to
the detailed description and to the drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
The specifics of the exclusive rights described herein are
particularly pointed out and distinctly claimed in the claims at
the conclusion of the specification. The foregoing and other
features and advantages of the embodiments of the invention are
apparent from the following detailed description taken in
conjunction with the accompanying drawings in which:
FIG. 1 depicts an exemplary biosensor according to embodiments of
the invention.
FIGS. 2A-2B depicts another exemplary biosensor according to
embodiments of the invention, in which:
FIG. 2A depicts a cross-sectional side view of the exemplary
biosensor, and
FIG. 2B depicts a top down view of the exemplary biosensor.
FIGS. 3A-3L depict an exemplary biosensor after various fabrication
operations according to embodiments of the invention, in which:
FIG. 3A illustrates the exemplary biosensor after a fabrication
operation according to embodiments of the invention;
FIG. 3B illustrates the exemplary biosensor after a fabrication
operation according to embodiments of the invention;
FIG. 3C illustrates the exemplary biosensor after a fabrication
operation according to embodiments of the invention;
FIG. 3D illustrates the exemplary biosensor after a fabrication
operation according to embodiments of the invention;
FIG. 3E illustrates the exemplary biosensor after a fabrication
operation according to embodiments of the invention;
FIG. 3F illustrates the exemplary biosensor after a fabrication
operation according to embodiments of the invention;
FIG. 3G illustrates the exemplary biosensor after a fabrication
operation according to embodiments of the invention;
FIG. 3H illustrates the exemplary biosensor after a fabrication
operation according to embodiments of the invention;
FIG. 3I illustrates the exemplary biosensor after a fabrication
operation according to embodiments of the invention;
FIG. 3J illustrates the exemplary biosensor after a fabrication
operation according to embodiments of the invention;
FIG. 3K illustrates the exemplary biosensor after a fabrication
operation according to embodiments of the invention;
FIG. 3L illustrates the exemplary biosensor after a fabrication
operation according to embodiments of the invention;
FIG. 4 depicts an exemplary biosensor according to embodiments of
the invention.
FIG. 5 depicts another exemplary biosensor according to embodiments
of the invention.
FIG. 6 depicts a flow diagram illustrating a method according to
one or more embodiments of the invention.
FIG. 7 depicts a flow diagram illustrating a method according to
one or more embodiments of the invention.
FIG. 8 depicts a computer system according to one or more
embodiments of the invention.
The diagrams depicted herein are illustrative. There can be many
variations to the diagram or the operations described therein
without departing from the spirit of the invention. For instance,
the actions can be performed in a differing order or actions can be
added, deleted or modified. Also, the term "coupled" and variations
thereof describes having a communications path between two elements
and does not imply a direct connection between the elements with no
intervening elements/connections between them. All of these
variations are considered a part of the specification.
In the accompanying figures and following detailed description of
the described embodiments, the various elements illustrated in the
figures are provided with two or three digit reference numbers.
With minor exceptions, the leftmost digit(s) of each reference
number correspond to the figure in which its element is first
illustrated.
DETAILED DESCRIPTION
For the sake of brevity, conventional techniques related to
semiconductor device and integrated circuit (IC) fabrication may or
may not be described in detail herein. Moreover, the various tasks
and process steps described herein can be incorporated into a more
comprehensive procedure or process having additional steps or
functionality not described in detail herein. In particular,
various steps in the manufacture of semiconductor devices and
semiconductor-based ICs are well known and so, in the interest of
brevity, many conventional steps will only be mentioned briefly
herein or will be omitted entirely without providing the well-known
process details.
Turning now to an overview of technologies that are more
specifically relevant to aspects of the invention, biosensors can
play an important role in the characterization of a variety of
different biomolecules. In neuroscience applications, for example,
bio sensors of different types can be used to detect
neurotransmitter function or to assess and investigate
abnormalities.
Several neurodegenerative diseases are associated with abnormal
neurotransmitter function. For example, Parkinson's disease can
result from a loss of dopamine secreting cells, and a resultant
decrease of dopamine, in the substantia nigra area of the brain.
Another neurotransmitter, glutamate (or glutamic acid), is
associated with and can play a key role in a number of neurological
disorders, including ischemia, schizophrenia, epilepsy, Alzheimer's
disease (AD), and Parkinson's disease (PD). Abnormal levels of
neurotransmitters, or accumulation of neurotransmitters in
particular regions, can signal abnormal function. Glutamate and
other neurotransmitters, such as dopamine, can send signals in the
brain and throughout the body. In the case of brain injury or
neurological disorders, for instance, glutamate can accumulate
outside of cells due to errors in glutamate transport or impaired
glutamate uptake.
Thus, neurotransmitter identity and location can provide important
information for the identification and characterization of a
variety of conditions. In addition, such information can provide
valuable information for treatment of neurological disorders and
illnesses because, for example, some of the primary medications
used to treat such conditions seek to change the effects of one or
more transmitters, such as dopamine.
Sensing of particular neurotransmitters can be accomplished in a
variety of ways, depending on the molecule and associated
properties in question. Biosensors can be categorized by type, for
example, such as calorimetric biosensors, potentiometric
biosensors, acoustic wave biosensors, resistivity biosensors,
amperometric biosensors, and optical biosensors.
The use and selection of biosensor type can depend, for example,
upon the method of metabolism of the neurotransmitter of interest.
Enzymatically controlled neurotransmitter metabolism can in some
cases be investigated by enzyme-based amperometric sensors.
Enzyme-based amperometric sensors can include an enzyme with
specificity toward a desired analyte embedded in a polymer on an
electrode. Such sensors can be formed, for example, by
electropolymerization of the enzyme and substrate around an
electrode, such as a metal electrode. After polymerization and
prior to use, the substrate can be removed from the sensor
providing an available binding site for substrate detection in
vivo.
Such amperometric sensors are known and can rely, for example, upon
electron generation through enzymatic oxidation of the analyte on
the electrode, which can result in measurable current. Glutamate
metabolism, for example, is enzymatically controlled and can have
an electrical current in decomposition, through the release of
electrons that are in proportion to its concentration. Related
measurements can be accomplished, for example by embedding
glutamate oxidase enzyme in a conformal polymer grown on a metal
electrode. In such implementations, electrical current can be used
to determine concentration of enzymatically metabolized
analytes.
Non-enzymatically controlled neurotransmitters can be measured with
resistivity-based methods. Dopamine metabolism, for instance, can
be measured without enzymatic binding. Dopamine and other
non-enzymatically controlled neurotransmitters can be detected and
measured, for example, by taking resistivity measurements from an
organic electrode imprinted with the target neurotransmitter. By
electropolymerizing a polymeric substrate with the desired analyte,
and then removing the analyte from the imprinted substrate, a
receptor cavity complimentary to the analyte can be generated in a
molecularly imprinted polymer (MIP). Such resistivity sensors are
known and can rely upon, for example, resistance changes in an
unbound versus an analyte-bound sensor. The measured resistivity in
such implementations can be proportional to the concentration of
the target analyte.
Conventional biosensors that can detect or measure a single
neurotransmitter provide only a limited view of neurological
processes and conditions. For example, a plurality of
neurotransmitters can each play a distinct and simultaneous role in
neurological impairments. Measurement of multiple neurotransmitters
can require the use of multiple sensing systems, which can be
cumbersome, cost-prohibitive, and could preclude time-sensitive or
time-dependent measurements of multiple analytes or measurement of
multiple analytes in the same region.
In addition, although some neurotransmitter activity occurs on the
micron and sub-micron scale, conventional biosensors can lack
precision needed to measure activity at that scale. Conventional
biosensors that can only measure on the scale of five to ten
microns, for example, cannot detect or sense neurotransmitters
across the surface of a single neuron, which measurements call for
nanometer scale resolution.
Aspects of the invention address the above-described shortcomings
of the prior art by providing a single device that can
simultaneously measure multiple biomolecules in the same region. In
some embodiments, multiple types of biosensors are included in a
single device. Embodiments of the invention include biosensors
capable of nanoscale resolution for sensing neurotransmitters.
Embodiments of the invention can include a large array of
nanopillars, wherein each nanopillar can be selectively wired to
allow distinct measurement from each pillar. Each pillar can be
formed or treated such that it is selective to a single
neurotransmitter. Embodiments of the invention include a plurality
of nanopillars formed of a conductive metal, such as gold or
platinum, wherein each nanopillar can be selectively coated with an
organic polymer that is sensitive to a particular target molecule.
In some embodiments of the invention, horizontal organic electrodes
associated with one or more nanopillars can, by measuring
resistivity, detect and/or characterize specific biomolecules. In
some embodiments of the invention, a sensor includes one or more
sensors, such as horizontal organic electrodes, for non-enzymatic
neurotransmitter detection and/or characterization and one or more
sensors for enzymatic neurotransmitter detection and/or
characterization. In some embodiments of the invention,
electrically functional nano-pillar electrodes are created across a
portion of a device substrate including structures of conductive
polymer between two or more electrodes. The conductive polymer can
include embedded molecular recognition sites. In some embodiments
of the invention a biosensor for multi-analyte detection is
implanted into a neural tissue region. Embodiments of the invention
can provide biomolecule concentration over time and for a specific
biomolecule type.
Turning now to a more detailed description of aspects of the
present invention, FIG. 1 depicts an exemplary structure 100 for
multi-analyte characterization according to embodiments of the
invention. The exemplary structure 100 can include a first sensing
region 110 and a second sensing region 120. The first sensing
region 110 and second sensing region 120 can include biosensors for
detecting different analytes. For example, in an exemplary
embodiment of the invention, a first sensing region 110 detects and
measures a first neurotransmitter, such as dopamine, and a second
sensing 120 region detects and measures a second neurotransmitter,
such as glutamate. The sensing regions 110, 120 can be connected to
a processor 106 through an interface layer 108. The processor is in
connection with an energy supply layer 104, such as a layer
including a battery or capacitor, and a communications interface
102, such as a graphical user interface.
Although FIG. 1 depicts two sensing regions, it is understood that
the number of sensing regions is not limited to two and can vary
depending upon the number and types of analytes to be measured. For
example, some embodiments of the invention can include tens or
hundreds of sensing regions.
Neurotransmitters and other analytes that can be detected or
measured according to embodiment of the invention include any
analyte suitable for the detection methods herein.
Analytes that can be detected with resistivity sensors can include
analytes that can be imprinted into a polymer matrix with suitable
selectivity and that can experience a change in resistivity upon
analyte binding. Such analytes can include, but are not limited to,
dopamine, epinephrine, ascorbic acid, and uric acid.
Analytes that can be detected with amperometric sensors can include
analytes that have associated enzymes that are amenable to matrix
immobilization without a loss in functionality and that can effect
a change in current, for instance through oxidization of the
analyte. For example, suitable enzymes for amperometric sensors can
include, but are not limited to, glutamate oxidase, lactate
oxidase, glucose oxidase, and choline oxidase. Enzymes for
amperometric sensors can be selected based upon the desired
analyte. Exemplary analytes that can be sensed with amperometric
sensors can include, but are not limited to, glutamate, lactate,
glucose, choline, adenosine, and gamma-amino-butyric acid
(GABA).
Biosensors according to embodiments of the invention can include
amperometric sensors and/or resistivity sensors. In some
embodiments of the invention, the structure includes a plurality of
amperometric sensors. In some embodiments of the invention, the
structure includes a plurality of resistivity sensors. In some
embodiments of the invention, the structure includes both
amperometric and resistivity sensors.
In some embodiments of the invention a structure includes a
plurality of amperometric sensors, wherein each of the plurality of
amperometric sensors detects the same analyte. In some embodiments
of the invention, a system includes different types of amperometric
sensors, in which different sensors are capable of sensing distinct
analytes. In some embodiments of the invention a structure includes
a plurality of amperometric sensors that detect two or more
different analytes.
In some embodiments of the invention a structure includes a
plurality of resistivity sensors, wherein each of the plurality of
resistivity sensors detects the same analyte. In some embodiments
of the invention, a system includes different types of resistivity
sensors, in which different sensors are capable of sensing distinct
analytes. In some embodiments of the invention a structure includes
a plurality of resistivity sensors that detect two or more
different analytes.
FIGS. 2A and 2B depict another exemplary structure 200 for
multi-analyte characterization according to one or more embodiments
of the present invention in which FIG. 2A is a cross-sectional side
view of the structure 200 and FIG. 2B is a top-down view of the
structure of FIG. 2A. The structure 200 can include a sensing layer
202. The sensing layer 202 can include multiple types of chemical
sensors 206, 208, 210, dispersed upon an interface layer 108. The
chemical sensors 206, 208, 210 can be in any pattern and any number
and can be tailored to the desired application. In some embodiments
of the invention, the sensing layer can include more than two
different types of chemical sensors. For example, in some
embodiments of the invention, the sensing layer can include three
different types of sensors (as shown in FIG. 2B) or, for example,
twenty different types of sensors (not shown). The chemical sensors
206, 208, 210 can be formed upon one or more nanopillars and can
include a single nanopillar structure or multiple nanopillar
structures (not shown in FIGS. 2A and 2B). The chemical sensors can
be spaced at a distance tailored to the desired application. In
some embodiments of the invention, the chemical sensors 206, 208,
210 are spaced apart from one another at a distance of about 200
nanometers (nm) to about 2 microns.
As is shown in FIG. 2B, the structure 200 can include a
microfluidic structure 204 surrounding the chemical sensors 206,
208, 210. In some embodiments of the invention, the microfluidic
structure 204 is in contact with some or all of the chemical
sensors. The structure 200 can also include a processor 106 in
communication with the sensing region 202 through an interface
layer 108. The processor is in connection with an energy supply
layer 104, such as a layer including a battery or capacitor, and a
communications interface 102, such as a graphical user
interface.
FIGS. 3A-3L depict an exemplary method of fabricating a sensor
according to one or more embodiments of the present invention.
FIG. 3A depicts a cross sectional side view of an exemplary
structure 300 after formation of a substrate 308 including a
plurality of nanopillars 302. The nanopillars 302 can each have a
base 306 and a pillar portion 304. The nanopillars 302 can be
formed on the substrate by depositing a resist layer, such as an
organic planarization layer (OPL) (not shown in FIG. 3A) on the
substrate 308, patterning holes in the resist layer with known
lithography techniques, and plating metal onto the structure 300 in
the holes in the resist layer. After plating the metal of the
nanopillars 302, the resist layer can be removed from the
structure. It is understood that although the exemplary structure
depicts three rows of nanopillars 302, the number of nanopillars
can vary and can be tailored to the desired application. For
example, in some embodiments of the invention a structure can
include tens or hundreds of rows of nanopillars 302.
In some embodiments of the invention, the nanopillars are spaced
apart at a pitch of about 200 nm to about 600 nm, such as about 200
nm to about 500 nm, or about 200 nm to about 400 nm, or about 200
nm to about 300 nm. In some embodiments of the invention, the
nanopillars can have a height of about 100 nm to about 1000 nm,
such as about 500 nm to about 800 nm. In some embodiments of the
invention, the nanopillars can have a diameter of about 50 nm to
about 100 nm.
FIG. 3B depicts a top down view of the exemplary structure 300
depicted in FIG. 3A showing an exemplary ordered arrangement of
nanopillars 302 formed on a substrate 308. In other embodiments of
the invention, not shown in FIG. 3B, unordered or irregularly
spaced nanopillars 302 can be formed on a substrate.
Nanopillars 302 can be formed of conductive metal, such as
platinum, gold, silver, nickel, palladium, tin, or copper. In some
embodiments of the invention, nanopillars 302 include platinum. In
some embodiments of the invention, nanopillars include copper.
The substrate 308 can include known semiconductor materials, such
as silicon (e.g., such as a silicon wafer), silicon germanium, or
other suitable rigid supporting material. Associated wiring (not
shown in FIG. 3A) can be fabricated using known processes, such as
conventional back end of the line technologies.
In some embodiments of the invention, after forming the nanopillars
302, the nanopillars can be lined with an insulating layer 304, as
is depicted in FIG. 3C. The insulating layer can include any known
insulating material suitable for semiconductor applications, such
as aluminum oxide, silicon oxide, or a composite of oxides. The
insulating layer 304 can be deposited on the structure 300, for
instance, by atomic layer deposition (ALD) using known
techniques.
In some embodiments of the invention, after lining the nanopillars
with an insulating layer 304, one or more resistivity sensors can
be formed on the structure. A resistivity sensor can be fabricated
by depositing an OPL layer 309 on the structure 300 and patterning
a hard mask layer 310 on the OPL layer 309, as is depicted in FIG.
3D. The OPL layer 309 can include, for instance, an organic spin-on
material. The hardmask layer 310 can be patterned such to expose
one or more nanopillars, such as two nanopillars, which can
function as part of a resistive sensor. The hardmask layer 310 can
include, for example, titanium and can have a thickness of about 20
nanometers.
After patterning the hardmask layer 310, the unmasked OPL layer 308
can be etched to expose a portion of insulating layer 304 on one or
more electrodes 302, as is illustrated in FIG. 3E. In some
embodiments of the invention, not shown in FIG. 3E, the unmasked
OPL layer 309 can be etched to expose all of the insulating layer
304 on one or more electrodes. Etching the OPL layer 309 can
include, for instance, reactive ion etch (RIE). The resulting
structure 300 can include one or more recessed areas for depositing
polymeric material.
After recessing the OPL layer 309, the structure can be wet etched,
for instance with dilute HF (DHF), to remove the portion of the
insulating layer 304 on the electrodes previously exposed through
etching the OPL layer 309, as is illustrated in FIG. 3F. In some
embodiments of the invention, upper portions 303 of a pair of
adjacent electrodes 302 are exposed through etching with DHF, as is
shown. In some embodiments of the invention, more than an upper
portion of the electrodes 302, for example, half of the vertical
height or all of the vertical height, is exposed through etching
with DHF (not shown in FIG. 3F).
The hard mask layer 310 can be removed from the structure 300 by
wet etching, for instance by wet etching with hydrogen peroxide.
FIG. 3G illustrates an exemplary structure 300 after removal of the
hard mask layer 310.
After removing the hard mask layer 310, remaining OPL layer 309 can
be removed from the structure 308. For example, OPL layer 309 can
be stripped from the structure 300 with plasma treatment, such as
O.sub.2 plasma or N.sub.2/H.sub.2 plasma etching. FIG. 3H depicts
an exemplary structure after removal of the OPL layer 309. As can
be seen in FIG. 3H, a resultant structure 300 can include adjacent
electrodes 312 that are partially exposed and partially coated with
insulating layer 304 and one or more fully insulated electrodes
314. Partially exposed electrodes 312 can serve as substrates for
electro-polymerized material to form resistivity sensors.
To form a resistivity sensor, a memory material 316 can be
electro-polymerized on the partially exposed electrodes 312, as is
shown in FIG. 3I. In some embodiments of the invention, voltage is
selectively applied to adjacent partially exposed electrodes 312
and the partially exposed electrodes 312 are exposed to a
conductive porous polymer precursor containing a desired template
molecule (analyte), such as dopamine. Polymer can grow on exposed
electrodes with applied voltage. In some embodiments of the
invention, multiple locations of a structure 300 include pairs of
adjacent partially exposed electrodes 312. In some embodiments of
the invention, polymerization voltages can be separately applied to
different pairs partially exposed electrodes 312 in the presence of
different desired template molecules. Thus, different locations of
a chip can be fabricated to be selective for different
analytes.
In some embodiments of the invention, the insulating layer 304 can
be removed from the structure, for instance by stripping with DHF.
FIG. 3J depicts an exemplary structure 300 after removal of the
insulating layer 304.
After forming a memory material 316 on the structure 300, the
template molecules can be removed to generate an imprinted polymer
318, for instance by washing the memory material or by cycling the
voltage of associated electrodes to dislodge the template molecules
from the conductive porous polymer. FIG. 3K depicts an exemplary
structure 300 including an imprinted polymer 318 and associated
electrodes 312. The resultant imprinted polymer 318 will have a
plurality of cavities, each having a size, shape, and binding
affinity (e.g., through hydrophobic interactions and the like)
specific to the template molecule, which can be the desired
analyte.
In some embodiments of the invention, one or more electrodes can be
functionalized along the length of the nanopillar, with differing
analyte sensitivity. In some embodiments of the invention, exposed
electrodes not associated with imprinted polymer 322 can be
associated with amperometric sensors. For example, in some
embodiments of the invention, a voltage can be selectively applied
to one or more nanopillars and the nanopillars exposed to
amperometric sensor polymer 320. Amperometric sensor polymer 320
can include conductive polymer embedded with an enzyme selective
for the desired analyte, such as glutamate oxidase. FIG. 3L depicts
an exemplary structure 300 after formation of an amperometric
sensor polymer 320 on a nanopillar. The amperometric sensor polymer
320 can be electropolymerized with both the enzyme and its
substrate (the desired analyte). After polymerization, the
substrate can be released from the polymer by washing or by
applying voltage to the nanopillar sufficient to release the
substrate, leaving an amperometric sensor polymer including a
plurality of enzymatic binding sites with affinity to the desired
analyte.
Exemplary conductive porous polymers that can be used to generate
the imprinted polymer 318 and amperometric sensor polymer 320 can
include, for instance, polyaniline with or without miscibility
additives, polypyrrole, or poly(3,4-ethylenedioxythiophene)
(PEDOT). Suitable miscibility additives can include, for example,
phytic acid, silicon nanoparticles, silicon oxide nanoparticles,
carbon nanoparticles, protobacteria proteins, including proteins
from the genus Geobacter, and the like.
FIG. 4 depicts an exemplary biosensor according to embodiments of
the invention. As is shown in FIG. 4, a structure 400 can include
both one or more resistivity sensors 402 and a plurality of
amperometric sensors 404, and 406. The structure can be selective
for a plurality of analytes, for instance by including an imprinted
polymer 408 selective for a first analyte, such as dopamine, a
first amperometric sensor 404 including a polymer embedded with a
first enzyme 410 and a second amperometric sensor 406 including a
polymer embedded with a second enzyme 412. The exemplary structure
400 includes a substrate 407, such as a silicon substrate. The
imprinted polymer 408 can be formed at an upper portion of the
associated nanopillars 414 providing accessible surfaces on a top
portion 415 and a bottom portion 417 of the imprinted polymer.
Providing an accessible bottom portion 417 of the imprinted polymer
408 can, for example, provide greater access and surface area to
detect analyte and, thereby, could provide greater sensitivity in
measurement relative, for example, to an imprinted polymer not
including an accessible bottom portion 417.
FIG. 5 depicts another exemplary biosensor according to embodiments
of the invention. As is shown in FIG. 5, a structure 400 can
include both one or more resistivity sensors 402 and a plurality of
amperometric sensors 404, and 406. The structure can be selective
for a plurality of analytes, for instance by including an imprinted
polymer 408 selective for a first analyte, such as dopamine, a
first amperometric sensor 404 including a polymer embedded with a
first enzyme 410 and a second amperometric sensor 406 including a
polymer embedded with a second enzyme 412. The exemplary structure
400 includes a substrate 407, such as a silicon substrate. As is
shown in FIG. 5, a resistivity sensor 408 can extend the length of
and encompass the associated nanopillars 414. In this embodiment of
the invention, the imprinted polymer 408 includes an accessible top
portion 415.
FIG. 6 depicts a flow diagram illustrating an exemplary method 600
according to one or more embodiments of the invention. The method
600 includes, as shown at block 602, forming nanopillars on a
substrate. The method 600 also includes, as shown at block 604,
lining the nanopillars with an insulating layer to generate a
plurality of lined nanopillars. The method 600 also includes, as
shown at block 606, removing the insulating layer from an upper
portion of a pair of adjacent nanopillars to generate exposed
adjacent nanopillars. The method 600 also includes, as shown at
block 608, forming a resistivity sensor on the exposed adjacent
nanopillars. The method 600 also includes, as shown at block 610,
removing the insulating layer from a lined nanopillar to generate
an exposed nanopillar. The method 600 also includes, as shown at
block 612, forming an amperometric sensor on the exposed
nanopillar.
FIG. 7 depicts a flow diagram illustrating an exemplary method 700
according to one or more embodiments of the invention. The method
700 includes, as shown at block 702, receiving a signal from a
multi-analyte sensor in contact with a biological tissue.
Biological tissue can include tissue containing one or more
analytes under investigation and can include, for instance,
neuronal tissue and/or brain tissue. The method 700 also includes,
as shown at block 704, determining a resistivity value from a
resistivity sensor. The resistivity value, for example, can be
proportional to the concentration of an analyte. The method 700
also includes, as shown at block 706, generating a concentration of
a first analyte based at least in part upon the resistivity value.
The method also includes determining an electrical current from an
amperometric sensor, as shown at block 708. The electrical current,
for example, can be proportional to the concentration of an
enzyme-active analyte. The method 700 also includes, as shown at
block 710, generating a concentration of a second analyte based at
least in part upon the electrical current.
Referring now to FIG. 8, a schematic of a computer system 800 is
shown according to a non-limiting embodiment. The cloud computer
system 800 is only one example of a suitable computer system and is
not intended to suggest any limitation as to the scope of use or
functionality of embodiments of the invention described herein.
Regardless, computer system 800 is capable of being implemented
and/or performing any of the functionality set forth
hereinabove.
Computer system 800 includes a computer system/server 12, which is
operational with numerous other general purpose or special purpose
computing system environments or configurations. Examples of
well-known computing systems, environments, and/or configurations
that can be suitable for use with computer system/server 12
include, but are not limited to, personal computer systems, server
computer systems, thin clients, thick clients, hand-held or laptop
devices, multiprocessor systems, microprocessor-based systems, set
top boxes, programmable consumer electronics, network PCs,
minicomputer systems, mainframe computer systems, and distributed
cloud computing environments that include any of the above systems
or devices, and the like.
Computer system/server 12 can be described in the general context
of computer system-executable instructions, such as program
modules, being executed by a computer system. Generally, program
modules can include routines, programs, objects, components, logic,
data structures, and so on that perform particular tasks or
implement particular abstract data types. Computer system/server 12
can be practiced in distributed cloud computing environments where
tasks are performed by remote processing devices that are linked
through a communications network. In a distributed cloud computing
environment, program modules can be located in both local and
remote computer system storage media including memory storage
devices.
As shown in FIG. 8, computer system/server 12 is shown in the form
of a general-purpose computing device. The components of computer
system/server 12 can include, but are not limited to, one or more
processors or processing units 16, a system memory 28, and a bus 18
that couples various system components including system memory 28
to processor 16.
Bus 18 represents one or more of any of several types of bus
structures, including a memory bus or memory controller, a
peripheral bus, an accelerated graphics port, and a processor or
local bus using any of a variety of bus architectures. By way of
example, and not limitation, such architectures include Industry
Standard Architecture (ISA) bus, Micro Channel Architecture (MCA)
bus, Enhanced ISA (EISA) bus, Video Electronics Standards
Association (VESA) local bus, and Peripheral Component Interconnect
(PCI) bus.
Computer system/server 12 typically includes a variety of computer
system readable media. Such media can be any available media that
is accessible by computer system/server 12, and it includes both
volatile and non-volatile media, removable and non-removable
media.
System memory 28 can include computer system readable media in the
form of volatile memory, such as random access memory (RAM) 30
and/or cache memory 32. Computer system/server 12 can further
include other removable/non-removable, volatile/non-volatile
computer system storage media. By way of example only, storage
system 34 can be provided for reading from and writing to a
non-removable, non-volatile magnetic media (not shown and typically
called a "hard drive"). Although not shown, a magnetic disk drive
for reading from and writing to a removable, non-volatile magnetic
disk (e.g., a "floppy disk"), and an optical disk drive for reading
from or writing to a removable, non-volatile optical disk such as a
CD-ROM, DVD-ROM or other optical media can be provided. In such
instances, each can be connected to bus 18 by one or more data
media interfaces. As will be further depicted and described below,
memory 28 can include at least one program product having a set
(e.g., at least one) of program modules that are configured to
carry out the functions of embodiments of the invention.
Program/utility 40, having a set (at least one) of program modules
42, can be stored in memory 28 by way of example, and not
limitation, as well as an operating system, one or more application
programs, other program modules, and program data. Each of the
operating system, one or more application programs, other program
modules, and program data or some combination thereof, can include
an implementation of a networking environment. Program modules 42
generally carry out the functions and/or methodologies of
embodiments of the invention as described herein.
Computer system/server 12 can also communicate with one or more
external devices 14 such as a keyboard, a pointing device, a
display 24, etc., one or more devices that enable a user to
interact with computer system/server 12, and/or any devices (e.g.,
network card, modem, etc.) that enable computer system/server 12 to
communicate with one or more other computing devices. Such
communication can occur via Input/Output (I/O) interfaces 22. Still
yet, computer system/server 12 can communicate with one or more
networks such as a local area network (LAN), a general wide area
network (WAN), and/or a public network (e.g., the Internet) via
network adapter 20. As depicted, network adapter 20 communicates
with the other components of computer system/server 12 via bus 18.
It should be understood that although not shown, other hardware
and/or software components could be used in conjunction with
computer system/server 12. Examples, include, but are not limited
to: microcode, device drivers, redundant processing units, external
disk drive arrays, RAID systems, tape drives, and data archival
storage systems, etc.
Various embodiments of the present invention are described herein
with reference to the related drawings. Alternative embodiments can
be devised without departing from the scope of this invention.
Although various connections and positional relationships (e.g.,
over, below, adjacent, etc.) are set forth between elements in the
following description and in the drawings, persons skilled in the
art will recognize that many of the positional relationships
described herein are orientation-independent when the described
functionality is maintained even though the orientation is changed.
These connections and/or positional relationships, unless specified
otherwise, can be direct or indirect, and the present invention is
not intended to be limiting in this respect. Accordingly, a
coupling of entities can refer to either a direct or an indirect
coupling, and a positional relationship between entities can be a
direct or indirect positional relationship. As an example of an
indirect positional relationship, references in the present
description to forming layer "A" over layer "B" include situations
in which one or more intermediate layers (e.g., layer "C") is
between layer "A" and layer "B" as long as the relevant
characteristics and functionalities of layer "A" and layer "B" are
not substantially changed by the intermediate layer(s).
The following definitions and abbreviations are to be used for the
interpretation of the claims and the specification. As used herein,
the terms "comprises," "comprising," "includes," "including,"
"has," "having," "contains" or "containing," or any other variation
thereof, are intended to cover a non-exclusive inclusion. For
example, a composition, a mixture, process, method, article, or
apparatus that comprises a list of elements is not necessarily
limited to only those elements but can include other elements not
expressly listed or inherent to such composition, mixture, process,
method, article, or apparatus.
Additionally, the term "exemplary" is used herein to mean "serving
as an example, instance or illustration." Any embodiment or design
described herein as "exemplary" is not necessarily to be construed
as preferred or advantageous over other embodiments or designs. The
terms "at least one" and "one or more" are understood to include
any integer number greater than or equal to one, i.e. one, two,
three, four, etc. The terms "a plurality" are understood to include
any integer number greater than or equal to two, i.e. two, three,
four, five, etc. The term "connection" can include an indirect
"connection" and a direct "connection."
References in the specification to "one embodiment," "an
embodiment," "an example embodiment," etc., indicate that the
embodiment described can include a particular feature, structure,
or characteristic, but every embodiment may or may not include the
particular feature, structure, or characteristic. Moreover, such
phrases are not necessarily referring to the same embodiment.
Further, when a particular feature, structure, or characteristic is
described in connection with an embodiment, it is submitted that it
is within the knowledge of one skilled in the art to affect such
feature, structure, or characteristic in connection with other
embodiments whether or not explicitly described.
For purposes of the description hereinafter, the terms "upper,"
"lower," "right," "left," "vertical," "horizontal," "top,"
"bottom," and derivatives thereof shall relate to the described
structures and methods, as oriented in the drawing figures. The
terms "overlying," "atop," "on top," "positioned on" or "positioned
atop" mean that a first element, such as a first structure, is
present on a second element, such as a second structure, wherein
intervening elements such as an interface structure can be present
between the first element and the second element. The term "direct
contact" means that a first element, such as a first structure, and
a second element, such as a second structure, are connected without
any intermediary conducting, insulating or semiconductor layers at
the interface of the two elements.
The phrase "selective to," such as, for example, "a first element
selective to a second element," means that the first element can be
etched and the second element can act as an etch stop.
The terms "about," "substantially," "approximately," and variations
thereof, are intended to include the degree of error associated
with measurement of the particular quantity based upon the
equipment available at the time of filing the application. For
example, "about" can include a range of .+-.8% or 5%, or 2% of a
given value.
As previously noted herein, for the sake of brevity, conventional
techniques related to semiconductor device and integrated circuit
(IC) fabrication may or may not be described in detail herein. By
way of background, however, a more general description of the
semiconductor device fabrication processes that can be utilized in
implementing one or more embodiments of the present invention will
now be provided. Although specific fabrication operations used in
implementing one or more embodiments of the present invention can
be individually known, the described combination of operations
and/or resulting structures of the present invention are unique.
Thus, the unique combination of the operations described in
connection with the fabrication of a semiconductor device according
to the present invention utilize a variety of individually known
physical and chemical processes performed on a semiconductor (e.g.,
silicon) substrate, some of which are described in the immediately
following paragraphs.
In general, the various processes used to form a micro-chip that
will be packaged into an IC fall into four general categories,
namely, film deposition, removal/etching, semiconductor doping and
patterning/lithography. Deposition is any process that grows,
coats, or otherwise transfers a material onto the wafer. Available
technologies include physical vapor deposition (PVD), chemical
vapor deposition (CVD), electrochemical deposition (ECD), molecular
beam epitaxy (MBE) and more recently, atomic layer deposition (ALD)
among others. Removal/etching is any process that removes material
from the wafer. Examples include etch processes (either wet or
dry), and chemical-mechanical planarization (CMP), and the like.
Semiconductor doping is the modification of electrical properties
by doping, for example, transistor sources and drains, generally by
diffusion and/or by ion implantation. These doping processes are
followed by furnace annealing or by rapid thermal annealing (RTA).
Annealing serves to activate the implanted dopants. Films of both
conductors (e.g., poly-silicon, aluminum, copper, etc.) and
insulators (e.g., various forms of silicon dioxide, silicon
nitride, etc.) are used to connect and isolate transistors and
their components. Selective doping of various regions of the
semiconductor substrate allows the conductivity of the substrate to
be changed with the application of voltage. By creating structures
of these various components, millions of transistors can be built
and wired together to form the complex circuitry of a modern
microelectronic device. Semiconductor lithography is the formation
of three-dimensional relief images or patterns on the semiconductor
substrate for subsequent transfer of the pattern to the substrate.
In semiconductor lithography, the patterns are formed by a light
sensitive polymer called a photo-resist. To build the complex
structures that make up a transistor and the many wires that
connect the millions of transistors of a circuit, lithography and
etch pattern transfer steps are repeated multiple times. Each
pattern being printed on the wafer is aligned to the previously
formed patterns and slowly the conductors, insulators and
selectively doped regions are built up to form the final
device.
The present invention may be a system, a method, and/or a computer
program product at any possible technical detail level of
integration. The computer program product may include a computer
readable storage medium (or media) having computer readable program
instructions thereon for causing a processor to carry out aspects
of the present invention.
The computer readable storage medium can be a tangible device that
can retain and store instructions for use by an instruction
execution device. The computer readable storage medium may be, for
example, but is not limited to, an electronic storage device, a
magnetic storage device, an optical storage device, an
electromagnetic storage device, a semiconductor storage device, or
any suitable combination of the foregoing. A non-exhaustive list of
more specific examples of the computer readable storage medium
includes the following: a portable computer diskette, a hard disk,
a random access memory (RAM), a read-only memory (ROM), an erasable
programmable read-only memory (EPROM or Flash memory), a static
random access memory (SRAM), a portable compact disc read-only
memory (CD-ROM), a digital versatile disk (DVD), a memory stick, a
floppy disk, a mechanically encoded device such as punch-cards or
raised structures in a groove having instructions recorded thereon,
and any suitable combination of the foregoing. A computer readable
storage medium, as used herein, is not to be construed as being
transitory signals per se, such as radio waves or other freely
propagating electromagnetic waves, electromagnetic waves
propagating through a waveguide or other transmission media (e.g.,
light pulses passing through a fiber-optic cable), or electrical
signals transmitted through a wire.
Computer readable program instructions described herein can be
downloaded to respective computing/processing devices from a
computer readable storage medium or to an external computer or
external storage device via a network, for example, the Internet, a
local area network, a wide area network and/or a wireless network.
The network may include copper transmission cables, optical
transmission fibers, wireless transmission, routers, firewalls,
switches, gateway computers and/or edge servers. A network adapter
card or network interface in each computing/processing device
receives computer readable program instructions from the network
and forwards the computer readable program instructions for storage
in a computer readable storage medium within the respective
computing/processing device.
Computer readable program instructions for carrying out operations
of the present invention may be assembler instructions,
instruction-set-architecture (ISA) instructions, machine
instructions, machine dependent instructions, microcode, firmware
instructions, state-setting data, configuration data for integrated
circuitry, or either source code or object code written in any
combination of one or more programming languages, including an
object oriented programming language such as Smalltalk, C++, or the
like, and procedural programming languages, such as the "C"
programming language or similar programming languages. The computer
readable program instructions may execute entirely on the user's
computer, partly on the user's computer, as a stand-alone software
package, partly on the user's computer and partly on a remote
computer or entirely on the remote computer or server. In the
latter scenario, the remote computer may be connected to the user's
computer through any type of network, including a local area
network (LAN) or a wide area network (WAN), or the connection may
be made to an external computer (for example, through the Internet
using an Internet Service Provider). In some embodiments,
electronic circuitry including, for example, programmable logic
circuitry, field-programmable gate arrays (FPGA), or programmable
logic arrays (PLA) may execute the computer readable program
instruction by utilizing state information of the computer readable
program instructions to personalize the electronic circuitry, in
order to perform aspects of the present invention.
Aspects of the present invention are described herein with
reference to flowchart illustrations and/or block diagrams of
methods, apparatus (systems), and computer program products
according to embodiments of the invention. It will be understood
that each block of the flowchart illustrations and/or block
diagrams, and combinations of blocks in the flowchart illustrations
and/or block diagrams, can be implemented by computer readable
program instructions.
These computer readable program instructions may be provided to a
processor of a general purpose computer, special purpose computer,
or other programmable data processing apparatus to produce a
machine, such that the instructions, which execute via the
processor of the computer or other programmable data processing
apparatus, create means for implementing the functions/acts
specified in the flowchart and/or block diagram block or blocks.
These computer readable program instructions may also be stored in
a computer readable storage medium that can direct a computer, a
programmable data processing apparatus, and/or other devices to
function in a particular manner, such that the computer readable
storage medium having instructions stored therein includes an
article of manufacture including instructions which implement
aspects of the function/act specified in the flowchart and/or block
diagram block or blocks.
The computer readable program instructions may also be loaded onto
a computer, other programmable data processing apparatus, or other
device to cause a series of operational steps to be performed on
the computer, other programmable apparatus or other device to
produce a computer implemented process, such that the instructions
which execute on the computer, other programmable apparatus, or
other device implement the functions/acts specified in the
flowchart and/or block diagram block or blocks.
The flowchart and block diagrams in the Figures illustrate possible
implementations of fabrication and/or operation methods according
to various embodiments of the present invention. Various
functions/operations of the method are represented in the flow
diagram by blocks. In some alternative implementations, the
functions noted in the blocks can occur out of the order noted in
the Figures. For example, two blocks shown in succession can, in
fact, be executed substantially concurrently, or the blocks can
sometimes be executed in the reverse order, depending upon the
functionality involved.
The descriptions of the various embodiments of the present
invention have been presented for purposes of illustration, but are
not intended to be exhaustive or limited to the embodiments
described. Many modifications and variations will be apparent to
those of ordinary skill in the art without departing from the scope
and spirit of the described embodiments. The terminology used
herein was chosen to best explain the principles of the
embodiments, the practical application or technical improvement
over technologies found in the marketplace, or to enable others of
ordinary skill in the art to understand the embodiments described
herein.
* * * * *
References